|InterMune Offers Added Data in Idiopathic Pulmonary Fibrosis, Endpoint Met; Karyopharm Announces Second Orphan Drug Designation for Selinexor|
|By Staff and Wire Reports|
|Tuesday, 20 May 2014 20:37|
InterMune, Inc. (NASDAQ: ITMN) today announced that results of analyses of pooled data from the ASCEND trial and the two previous Phase 3 CAPACITY trials evaluating pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) were presented at the 2014 International Conference of the American Thoracic Society (ATS) in San Diego, Calif. In addition, long-term safety results in patients with IPF receiving treatment with pirfenidone for a median duration of 2.6 years and a maximum duration of 7.7 years were published in the current edition of the journal Respirology. Pirfenidone is not approved for sale in the United States.
Exploratory Analyses of Pooled Data from ASCEND and CAPACITY New efficacy results from analyses conducted on the pooled population from the ASCEND trial and the two previous Phase 3 CAPACITY studies (004 and 006), in addition to the previously reported results of the Phase 3 study ASCEND and the prespecified pooled analyses of mortality, were presented at the ATS Symposium "Skyfall: Late Breaking Trials in Idiopathic Pulmonary Fibrosis." The similar study designs, patient populations and clinical efficacy outcomes across these three independent global Phase 3 studies justify the pooling of study results, allowing a comprehensive analysis of outcomes from a large data set (N = 1,247). The primary objective of these new analyses of the prespecified primary and secondary efficacy endpoints in ASCEND, conducted on the large pooled population, is to provide a more precise estimate of the magnitude of the pirfenidone treatment effect. Pooled analyses were conducted at Week 52, the time of the primary endpoint assessment in ASCEND, and also at Week 72, the time of the primary endpoint assessment in CAPACITY. These Week 72 analyses provide insight into the persistence of the pirfenidone treatment effect.
These analyses were presented by Dr. Talmadge King, Professor and Chair, Department of Medicine, University of California, San Francisco and Co-chair of the ASCEND protocol steering committee, and complement earlier reports about the ASCEND or CAPACITY studies alone. Earlier at ATS, the ASCEND study was featured in the New England Journal of Medicine's symposium and published on-line in the New England Journal of Medicine on May 18. The ASCEND data will be published in the journal's May 29 print issue.
Results of ASCEND were the subject of a May 18 investor press release and webcast and therefore won't be commented on in this press release.
Pooled Analyses at One Year -- Forced Vital Capacity (FVC) The magnitude of treatment effect of pirfenidone on FVC across all three Phase 3 studies was measured by comparing the proportion of patients in the pirfenidone and placebo groups experiencing either a clinically meaningful change in FVC or death. A 10% decline in FVC in an individual IPF patient is considered clinically meaningful and predictive of mortality. At one year, the pooled analysis showed that compared to placebo, pirfenidone reduced by 43.8% the proportion of patients who experienced a meaningful decline in FVC or death (rank ANCOVA p<0.0001).
6-Minute Walk Distance (6MWD), Progression-Free Survival (PFS) and Dyspnea Several secondary endpoints, including change from baseline in 6MWD, PFS, and dyspnea, were analyzed in the pooled population. 6MWD is a measure of exercise tolerance, and a 50-meter decrement in walk distance is an independent predictor of mortality in an individual patient with IPF. At one year, the pooled analysis showed that compared to placebo, pirfenidone reduced by 28.7% the proportion of patients who experienced a decline in 6MWD of 50 meters or greater or died (rank ANCOVA p=0.0004).
PFS is a measure of time before death or disease-progression. Disease progression was defined as a percent predicted FVC decrement of 10% or greater or 6MWD decrement of 50 meters or greater. At one year, the pooled analysis showed that compared to placebo, pirfenidone reduced the risk of death or disease progression by 38% (Hazard Ratio [HR] 0.62; 95% confidence interval [CI], 0.51-0.75; p<0.0001).
An analysis of dyspnea (shortness of breath) in the pooled population showed a difference favoring pirfenidone at one year; 24.0% of patients in the pirfenidone group experienced a >20 point worsening in UCSD SOBQ score or death, compared with 31.4% of patients in the placebo group (relative difference, 23.7%; p=0.0471). There was no significant difference between groups in dyspnea scores in any of the individual studies.
Mortality As reported on May 18, at Week 52, the pre-specified analysis from the ASCEND study of the pooled population of the ASCEND and CAPACITY trials showed that the risk of all-cause mortality was reduced by 48% in the pirfenidone group compared to the placebo group (HR 0.52, log rank p=0.0107). Additionally, the risk of treatment-emergent IPF-related death in the pirfenidone group compared to placebo was reduced by 68% (HR 0.32, log rank p=0.0061).
Exploratory Week 72 Pooled Analyses Analyses of the following clinical outcomes were performed on the pooled data from the ASCEND and CAPACITY studies through 72 weeks (the CAPACITY endpoint). These analyses showed a magnitude of treatment effect of pirfenidone in the range of 43% to 57% and were statistically significant favoring pirfenidone:
o FVC decline >/= 10% or death o Progression-free survival o All-cause mortality o Treatment-emergent all-cause mortality o IPF-related mortality o Treatment-emergent IPF-related mortality
Pooled Phase 3 Safety Analyses In the pooled Phase 3 data set of ASCEND and CAPACITY, the profiles of adverse events (AEs) (treatment-emergent, Grade 3 or 4), serious adverse events (SAEs) and AEs leading to discontinuation were similar to those observed in ASCEND alone as were reported in the company's press release of May 18.
Long-term Pirfenidone Safety Data Published in Respirology A comprehensive assessment of the long-term safety and tolerability of pirfenidone in patients with IPF was performed in an integrated population from four clinical trials (n=789) evaluating pirfenidone in patients with IPF. The results of this analysis were reported on May 18 in the journal Respirology. All patients who were randomized to treatment with pirfenidone 2403 mg/d in the Phase 3 CAPACITY studies (Studies 004 and 006) and all patients who received at least one dose of pirfenidone in one of two ongoing open-label studies (Studies 002 and 012) in patients with IPF were included in the analysis. Safety outcomes were evaluated from baseline until 28 days after the last dose of study drug.
According to the published study, the comprehensive safety and tolerability analysis demonstrated that treatment with pirfenidone for up to 7.7 years presented a favorable safety profile and was generally well tolerated. The median duration of exposure to pirfenidone was 2.6 years (range, 1 week–7.7 years) and the cumulative total exposure was 2,059 person exposure years (PEY). Gastrointestinal and skin-related events were the most commonly reported adverse events. These included nausea (40%), dyspepsia (21%), vomiting (18%) and rash (26%). These events were generally mild to moderate in severity, decreased in incidence over the first several months of therapy and rarely led to treatment discontinuation.
"Our long-term safety analysis is extremely robust given the large study population and overall duration of treatment exposure, which is unique for novel agents for orphan diseases," said Dominique Valeyre M.D., of the Hôpital Avicenne, Bobigny, France, and lead author of the Respirology paper. "These data provide further evidence to support the long-term clinical use of pirfenidone in patients with idiopathic pulmonary fibrosis."
Analysis of new onset adverse events by 6-month intervals demonstrated that gastrointestinal and skin-related adverse events tended to occur early in the course of treatment. The incidence of new onset gastrointestinal and skin-related events declined after the first 6 months and remained low during subsequent intervals.
Elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) of more than three times the upper limit of normal (3 X ULN) occurred in 2.7% of patients. The adjusted incidence of AST/ALT elevations was 1.7 per 100 PEY. These elevations were generally transient, reversible, and without significant clinical consequence.
Worsening IPF (8.7%) was the most common event leading to treatment discontinuation. The only other adverse events that resulted in treatment discontinuation in >1% of patients were nausea (2.3%), rash (1.6%), and respiratory failure (1.3%).
A total of 18.8% patients died during the period of observation. Treatment-emergent deaths, defined as deaths occurring after the first dose and within 28 days of the last dose of study drug, occurred in 15.6% of patients; of these, 11.2% were assessed by the investigator as IPF-related. The adjusted incidence of treatment emergent death, defined as treatment emergent deaths per 100 PEY, was 6.0 for all-cause death and 4.3 for IPF-related death.
Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the treatment of cancer and other major diseases, today announced that its lead drug candidate, Selinexor (KPT-330), has received orphan drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of Diffuse Large B-Cell Lymphoma (DLBCL). The designation is designed to encourage the development of drugs which may provide significant benefit to patients suffering from rare diseases.
"The granting of Orphan Drug Designation by the FDA for DLBCL is another significant milestone in the Selinexor development program," commented Dr. Sharon Shacham, Founder, CSO and President of Karyopharm. "There are limited treatment options for patients with relapsed or refractory DLBCL, with no new agents approved for this indication over the past two decades. Many patients relapse after responding to multi-agent first-line therapy. The fundamental treatment of DLBCL has changed little in the past two decades, with no new or targeted agents approved for this indication. Accordingly, we are excited about the prospects for Selinexor's novel mechanism of action to potentially treat this patient population, either alone or in combination with other therapies."
Orphan designation by the FDA is granted to promote the development of drugs that target conditions affecting 200,000 or fewer U.S. patients annually and that are expected to provide significant therapeutic advantage over existing treatments. Orphan designation qualifies a company for benefits that apply across all stages of drug development, including an accelerated approval process, seven years of market exclusivity following marketing approval, tax credits on U.S. clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.
Michael G. Kauffman, MD, PhD, Karyopharm's Chief Executive Officer said, "We are encouraged by the response data in patients with DLBCL who have received Selinexor in our ongoing Phase 1 clinical trial in advanced hematological malignancies. We look forward to the commencement of additional trials in patients with DLBCL, including a registration-directed clinical trial of Selinexor and investigator-sponsored combination studies of Selinexor. We plan to present updated clinical data for Selinexor across multiple indications, including DLBCL, at ASCO 2014."
Diffuse large B-cell lymphoma, or DLBCL, is a form of Non-Hodgkin lymphoma, or NHL, and is the most common of the aggressive NHLs, accounting for up to 30% of newly-diagnosed cases of NHL in the United States. According to the American Cancer Society, about 70,800 patients will be diagnosed with NHL in the United States in 2014 and an estimated 18,990 patients will succumb to the disease. Accordingly, approximately 21,000 patients will be diagnosed with DLBCL in the United States in 2014. In patients who are less than 65 years old, and who have good organ function, high dose chemotherapy with stem cell transplantation can lead to cures in approximately 50% of these patients. Older patients relapsing after initial chemotherapy, and those relapsing after stem cell transplantation, have a very poor prognosis, and the expected survival of such patients is less than one year.
Caribbean International Holdings (Pink Sheets:CIHN) through its subsidiary, Regenerative BioScience, Inc., announced today that during the World Congress in Orlando, FL this past weekend, the Company's Advisory Board Member, Rafael Gonzalez, Ph.D., speech to the attendees at the World Congress was widely acclaimed and helped further enhance the Company's increasing image in the field of regenerative medicine.
Chimerix, Inc. (Nasdaq:CMRX), a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, today announced the pricing of an underwritten public offering of 7,300,000 shares of its common stock at a price to the public of $14.22 per share.
FutureWorld (OTCQB: FWDG), a U.S. Diversified Holding Company formed to capitalize on the burgeoning markets globally, announces today that its subsidiary HempTechRx has launched its very own brand of sophisticated vaporizer called URVape ™. URVape ™ is initially marketed and sold online at; http://www.urvape.com.
Immunomedics, Inc., (Nasdaq:IMMU) today reported a stabilization of disease, as measured by computed tomography (CT) according to RECIST criteria, in pancreatic cancer patients with advanced disease and who failed 1-5 prior therapies. In a group of 13 CT-assessable patients receiving repeated doses of the Company's investigational antibody-drug conjugate (ADC), IMMU-132, a median time-to-progression of 12.7 weeks was reported (range 4.3-21.4 weeks), which is better than the median 8.0 weeks (range 4-36 weeks) estimated from their last prior therapy.
MediWound Ltd. (Nasdaq:MDWD), a fully-integrated, biopharmaceutical company bringing innovative therapies to address unmet needs in severe burn and wound management, announces the successful completion of a Good Manufacturing Practice (GMP) audit of the Company's facility in Yavne, Israel by the Israeli Ministry of Health (IMOH).
Myriad Genetics, Inc. (Nasdaq:MYGN) today presented new data from a clinical validation study of Prolaris at the 2014 American Urological Association (AUA) Annual Meeting in Orlando, Fla.
NeuroBioPharm a Neptune Technologies & Bioressources Inc. subsidiary (Nasdaq:NEPT) (TSX:NTB) announces the resignation of Frederic Harland as Chief Financial Officer of NeuroBio with immediate effect.
Prosensa Holding N.V. (Nasdaq:RNA), the Dutch biopharmaceutical company focusing on RNA-modulating therapeutics for rare diseases with high unmet need, today reported financial results for the first quarter ending March 31, 2014 and provided an update on the next steps for its exon-skipping platform for the treatment of Duchenne Muscular Dystrophy (DMD).
Relypsa, Inc. (Nasdaq:RLYP), a biopharmaceutical company, today announced that it has entered into a multi-year commercial manufacturing and supply agreement with DSM Fine Chemicals Austria NFG GMBH & Co. KG for the active pharmaceutical ingredient for patiromer, the company's novel polymer in development for the treatment of hyperkalemia. DSM Fine Chemicals is a business unit of the newly formed DPx Holding B.V. which also owns Patheon Pharma Services and Banner Life Sciences.
SANUWAVE Health, Inc. (OTCBB:SNWV) today received a patent issued by the U.S. Patent and Trademark Office entitled "Use of Pressure Waves for Stimulation, Proliferation, Differentiation and Post-Implantation Viability of Stem Cells."
Stemline Therapeutics, Inc. (Nasdaq:STML) announced today that data demonstrating SL-401 efficacy in multiple myeloma (MM) preclinical models will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting being held May 30-June 3, 2014 in Chicago, IL.